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Culture environment regulates amino acid turnover and glucose utilisation in human ES cells

journal contribution
posted on 2023-05-17, 21:50 authored by Rathjen, J, Yeo, C, Yap, C, Tan, BSN, Rathjen, PD, Gardner, DK
Human embryonic stem (ES) cells have been proposed as a renewable source of pluripotent cells that can be differentiated into various cell types for use in research, drug discovery and in the emerging area of regenerative medicine. Exploitation of this potential will require the development of ES cell culture conditions that promote pluripotency and a normal cell metabolism, and quality control parameters that measure these outcomes. There is, however, relatively little known about the metabolism of pluripotent cells or the impact of culture environment and differentiation on their metabolic pathways. The effect of two commonly used medium supplements and cell differentiation on metabolic indicators in human ES cells were examined. Medium modifications and differentiation were compared in a chemically defined and feeder-independent culture system. Adding serum increased glucose utilisation and altered amino acid turnover by the cells, as well as inducing a small proportion of the cells to differentiate. Cell differentiation could be mitigated by inhibiting p38 mitogen-activated protein kinase (p38 MAPK activity). The addition of Knockout Serum Replacer also increased glucose uptake and changed amino acid turnover by the cells. These changes were distinct from those induced by serum and occurred in the absence of detectable differentiation. Induction of differentiation by bone morphogenetic protein 4 (BMP4), in contrast, did not alter metabolite turnover. Deviations from metabolite turnover by ES cells in fully defined medium demonstrated that culture environment can alter metabolite use. The challenge remains to understand the impact of metabolic changes on long-term cell maintenance and the functionality of derived cell populations.

History

Publication title

Reproduction, Fertility and Development

Volume

26

Issue

5

Pagination

703-716

ISSN

1031-3613

Department/School

Menzies Institute for Medical Research

Publisher

C S I R O Publishing

Place of publication

Australia

Rights statement

Journal compilation copyright 2013 CSIRO

Repository Status

  • Restricted

Socio-economic Objectives

Expanding knowledge in the biological sciences

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